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Membranous nephropathy, interstitial nephritis, and Fanconi syndrome-- glomerular antigen
S P Makker1, R Widstrom, J Huang
1Department of Pediatrics, University of California, Davis Medical Center, Sacramento 95817, USA.
Abstract:
We characterized the glomerular antigen of membranous nephropathy (MN) in a child with the triad of MN, proximal renal tubular basement membrane autoantibody (TBMAb)-associated interstitial nephritis (ITN), and Fanconi syndrome. Granular staining was demonstrated for human gp600 in the vicinity of immune deposits of MN along glomerular capillary loops, using a monospecific polyclonal antibody to human gp600 by indirect immunofluorescence. However, no staining was observed in the MN deposits for receptor-associated protein. Membranous nephropathy preceded the development of TBMAbs, ITN, and Fanconi syndrome by 1 year, showing that the MN lesion does not result from the initial immunological injury to the tubulointerstitium, as postulated earlier. We confirmed the reactivity of TBMAbs with the recently described rabbit 58-kilodalton (kDa) tubular basement membrane antigen (TBMAg). However, this is the first report to show reactivity of these antibodies with the human 58-kDa protein. Also, we found that TBMAg is comprised of a single protein band of 58 kDa, unlike the previously described combination of two protein band (58 kDa and 175 kDa). In this patient, following prednisone treatment, the TBMAbs became undetectable, and the nephrotic syndrome and Fanconi syndrome resolved, thus suggesting a causal role of TBMAbs in the pathogenesis of Fanconi syndrome. We postulate that in this rare disorder, renal lesions result from an autoimmune response to the 58-kDa TBMAg and possibly to gp600, and that the predisposition to autoimmunity is genetically linked to the HLA B7 serotype.
Insights
This study identifies gp600 and a 58-kDa tubular basement membrane antigen (TBMAg) as potential targets in a child with membranous nephropathy and Fanconi syndrome. Autoantibodies to TBMAg may cause Fanconi syndrome, with HLA B7 linkage suggested.
Area of Science:
- Nephrology
- Immunology
- Genetics
Background:
- Membranous nephropathy (MN) can coexist with autoimmune tubulointerstitial nephritis (ITN) and Fanconi syndrome.
- The glomerular antigen in MN and the target antigen in TBMAb-associated ITN are not fully elucidated.
- Previous hypotheses suggested ITN precedes MN, but this case challenges that timeline.
Observation:
- A child presented with a triad of MN, TBMAb-associated ITN, and Fanconi syndrome.
- Human gp600 showed granular staining near MN immune deposits, but not receptor-associated protein.
- The patient's MN developed a year before TBMAbs, ITN, and Fanconi syndrome.
- Antibodies (TBMAbs) reacted with a human 58-kDa protein, identified as the tubular basement membrane antigen (TBMAg).
- Unlike previous reports, human TBMAg appeared as a single 58-kDa band.
Findings:
- Membranous nephropathy (MN) was identified as preceding the autoimmune tubulointerstitial nephritis (ITN) and Fanconi syndrome.
- The study confirmed TBMAb reactivity with the human 58-kDa tubular basement membrane antigen (TBMAg).
- Prednisone treatment led to undetectable TBMAbs and resolution of nephrotic and Fanconi syndromes, suggesting a causal role for TBMAbs.
Implications:
- This case suggests an autoimmune response to 58-kDa TBMAg and potentially gp600 in this rare disorder.
- The findings challenge the previous notion that ITN initiates MN.
- Genetic predisposition linked to HLA B7 serotype may play a role in the development of these autoimmune renal diseases.